Efficient transformation of CO2 into quinazoline-2,4(1: H,3 H)-diones at room temperature catalyzed by a ZnI2/NEt3 system

Article abstract of DOI:10.1039/c9nj04302k

The readily available ZnI₂/NEt₃ system was used firstly to catalyze the transformation of CO₂ and 2-aminobenzonitriles into quinazoline-2,4(1H,3H)-diones at room temperature and low CO₂ pressure in high yields. Further experiments indicated that this ZnI₂/NEt₃ system has excellent effects on activating both amino and cyano groups.

Full text of DOI:10.1039/c9nj04302k

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Efficient transformation of CO2 into quinazoline-
2,4(1H,3H)-diones at room temperature catalyzed
by a ZnI2/NEt3 system†
Cite this: New J. Chem., 2019,
43, 16164
Shangqing Chen,a Zheng Wang,a Jiayin Hu, *a Yafei Guoa and
ab
Tianlong Deng
*
Received 20th August 2019,
Accepted 17th September 2019
The readily available ZnI2/NEt3 system was used firstly to catalyze the transformation of CO2 and
2-aminobenzonitriles into quinazoline-2,4(1H,3H)-diones at room temperature and low CO2 pressure in
high yields. Further experiments indicated that this ZnI2/NEt3 system has excellent effects on activating
both amino and cyano groups.
DOI: 10.1039/c9nj04302k
rsc.li/njc
Introduction
Carbon dioxide (CO2) is deemed to be one of the most inexpensive,
nontoxic, renewable and readily available C1 resources. The
chemical fixation and transformation of CO2 into value-added
organic molecules can both retard global warming and diminish
the energy crisis, which is highly desirable due to its economic
and environmental benefits.1–4 However, because of its inherent
thermodynamic stability and kinetically inert nature,5,6 both
harsh reaction conditions such as high temperature and CO2
pressure and complex catalysts are often required for efficient
CO2 conversion.7–9 Therefore, the efficient conversion of CO2
under mild conditions with easily available and high-efficiency
catalysts is still desirable but challenging.
Scheme 1 Reaction of CO2 and 2-aminobenzonitrile to form quinazoline-
2,4(1H,3H)-dione catalyzed by ZnI2/NEt3.
and supported task-specific ionic liquids20–24 have been reported
to efficiently promote the synthesis of quinazoline-2,4(1H,3H)-
diones, even under mild conditions; however, these routes also
suffer from problems, such as complex synthetic procedures and
the high cost of ILs. Therefore, the development of highly
efficient, inexpensive and easily available catalysts for the con-
version of CO2 with 2-aminobenzonitriles under mild conditions is
still imperative and challenging.
In this work, the ZnI2/triethylamine (NEt3) system was used
firstly to catalyze the reactions of CO2 and 2-aminobenzonitriles
to quinazoline-2,4(1H,3H)-diones (Scheme 1). It was found that
the inexpensive and readily available Zn-containing basic
catalyst system could effectively promote the reaction at room
temperature and low CO2 pressure, and high yields of value-added
quinazoline-2,4(1H,3H)-diones were obtained. The mechanism
exploration indicated that this ZnI2/NEt3 system has excellent
effects on activating both amino and cyano groups.
Quinazoline-2,4(1H,3H)-diones are a class of heterocyclic
compounds that play important roles in pharmaceutical and
biotechnology industries.10–12 Among the developed synthetic
routes for quinazoline-2,4(1H,3H)-diones, the atom-economical
reaction of CO2 with 2-aminobenzonitriles has attracted much
attention. Common organic and inorganic strong bases, including
1,8-diazabicyclo[5.4.0]undec-7-ene (DBU),13 1,1,3,3-tetramethyl
16
guanidine (TMG),14 N-heterocyclic carbene,15 Cs2CO3 and
MgO–ZrO2,17 can catalyze this reaction; meanwhile, most of
these bases are expensive and unrecyclable. Green and readily
available water18 and salt lake brines19 can also promote this
reaction; however, harsh and severe reaction conditions, especially
high temperature, are needed. Recently, various homogeneous
Experimental
Chemicals
a Tianjin Key Laboratory of Brine Chemical Engineering and Resource
Eco-utilization, College of Chemical Engineering and Materials Science,
Tianjin University of Science and Technology, Tianjin 300457, China.
E-mail: hujiayin@tust.edu.cn, tldeng@tust.edu.cn; Tel: +86-22-60602963
b College of Marine and Environmental Science, Tianjin University of Science and
Technology, Tianjin 300457, China
CO2 with a purity of 99.99% was supplied by Tianjin Feilin
Gases Co., Ltd. 2-Aminobenzonitrile (98%), 2-amino-5-chloro-
benzonitrile (98%) and zinc iodide (98%) were supplied by
† Electronic supplementary information (ESI) available. See DOI: 10.1039/c9nj04302k 3A Chemicals Ltd. 2-Amino-4-chlorobenzonitrile (99%) was
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Table 1 Reaction of 2-aminobenzonitrile 1a and CO2 in the presence of
various catalystsa
purchased from Tokyo Chemical Inorganic Co., Ltd. 2-Amino-
4,5-dimethoxybenzonitrile (99%) was purchased from Fluoro-
chem Ltd. 2-Amino-5-bromobenzonitrile (99%) was supplied by
J&K Scientific Ltd. Triethylamine (NEt3, 99%) was obtained
from Aladdin. The deuterated solvent (DMSO-d6) was obtained
from Cambridge Isotope Laboratories, Inc. All the chemicals were
commercially available and were used without further purification.
Catalytic reaction
Entry
Catalyst(s)
Yieldb (%)
As an example, the procedure using 2-aminobenzonitrile as the
substrate is described, and those for other substrates were
similar. In a typical experiment, 2-aminobenzonitrile (2 mmol,
0.2643 g), ZnI2 (0.6 mmol, 0.6384 g), NEt3 (2 mmol, 0.2024 g)
and 0.2 mL toluene were loaded into a 22 mL stainless-steel
batch reactor equipped with a magnetic stirrer. The air in
the reactor was removed by blowing CO2 through the reactor.
Then, the desired pressure of CO2 was charged into the reactor
and the reactor was sealed. The reactor was placed in an oil bath
at the desired temperature, and the mixture was stirred. After the
reaction, the excess CO2 in the reactor was released slowly.
Subsequently, 15 mL water was added to the reactor, and the
mixture was centrifuged to precipitate the product. The product
was then washed with tert-butyl methyl ether (3 Â 15 mL) and
ethyl alcohol (2 Â 15 mL) and dried at 90 1C for 3 h. Finally, the
mass of the product was measured by an electronic balance, and
the isolated yield was calculated from 2-aminobenzonitrile. The
purified products were characterized by NMR spectroscopy.
1H NMR and 13C NMR studies were carried out with a Bruker
NMR spectrometer with [D6]DMSO as the solvent.
1
2
3
4
5
6
7
8
—
ZnI2
NEt3
0
0
o1
15
3
20
25
1
Zn(OAc)2/NEt3
Zn(C6H11O7)2/NEt3
ZnCl2/NEt3
ZnBr2/NEt3
KI/NEt3
ZnI2/NEt3
ZnI2/NEt3
9
58
97
10c
a
Reaction conditions: 2 mmol of 1a, 2 mmol of NEt3, 0.6 mmol of
b
c
catalyst, 0.2 mL toluene, 1 MPa CO2, 30 1C, 6 h. Isolated yield. The
reaction time was 21 h.
dissociation capacity with Zn(II),25 which may increase the reactivity
of Zn(II). Thus, ZnI2 showed the highest catalytic activity, and the
ZnI2/NEt3 catalyst system could effectively promote the reaction,
affording a 97% yield of 2a within 21 h.
Effects of the reaction conditions
Subsequently, the effects of the molar ratios of ZnI2 and NEt3
on the reaction over the ZnI2/NEt3 system were also respectively
investigated, and the results are shown in Fig. 1. It was shown
that the yields depended strongly on the molar ratios of ZnI2
and NEt3. The yield could reach 97% at a ZnI2 molar ratio of
30% and a NEt3 molar ratio of 100%; this result indicated the
significant roles of ZnI2 and NEt3 in catalyzing the reaction.
We further studied the effects of CO2 pressure, and the
dependence of the yield of 2a on CO2 pressure is given in
Fig. 2a. As expected, the yield of 2a increased with increasing
CO2 pressure at the beginning, and a yield of 97% could be
achieved at 1 MPa CO2. No further increase in the yield was
observed with increased CO2 pressure, suggesting that 1a was
Results and discussion
Screening of catalysts
Firstly, the catalytic activities of various catalytic systems were
tested using the conversion of CO2 and 2-aminobenzonitrile
(1a) to quinazoline-2,4-(1H,3H)-dione (2a) as a model reaction
at 30 1C and 1 MPa CO2; the results are given in Table 1. It was
found that the reaction did not occur in the absence of any
catalyst (Table 1, entry 1), as well as in the presence of individual
ZnI2 or NEt3 (Table 1, entries 2 and 3). In the presence of NEt3,
different zinc salts, including Zn(OAc)2, Zn(C6H11O7)2, ZnCl2,
ZnBr2 and ZnI2, were also investigated, and all of them could
promote this reaction with yields of the target product 2a
ranging from 3% to 58% in 6 h (Table 1, entries 4–7 and 9).
Interestingly, the catalytic activities of the halogen-based zinc
salt/NEt3 systems were better than those of the oxygen acid-
based zinc salt/NEt3 systems, and the catalytic yields of the zinc
halides followed the order: ZnI2 4 ZnBr2 4 ZnCl2; this
indicates that the halide ions, especially IÀ, may be crucial for
the high catalytic activity of the zinc halide/NEt3 system. In
order to confirm the role of IÀ, the activity of a KI/NEt3 system
was also screened. However, the KI/NEt3 system had low catalytic
activity for the reaction (Table 1, entry 8). This result indicates
that compared with IÀ, Zn(II) plays a more important role in
this reaction. Compared with other halide ions, IÀ has stronger
Fig. 1 Dependence of the yield on the molar ratios of ZnI2 and NEt3.
Reaction conditions: (a) 2 mmol of 1a, 2 mmol of NEt3, 0.2 mL toluene,
30 1C, 1 MPa CO2, 21 h and different molar ratios of ZnI2; (b) 2 mmol of 1a,
0.6 mmol of ZnI2, 0.2 mL toluene, 30 1C, 1 MPa CO2, 21 h and different
molar ratios of NEt3. Isolated yields.
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Table 2 Scope of the 2-aminobenzonitrile substrates for the reactions
under optimized conditionsa
Entry
1
Substrate
Product
t (h)
Yieldb (%)
97
21
2
3
4
21
30
30
64
95
Fig. 2 Dependence of the yields on pressure and reaction time. Reaction
conditions: (a) 2 mmol of 1a, 0.6 mmol of ZnI2, 2 mmol of NEt3, 0.2 mL
toluene, 30 1C, 21 h and different CO2 pressures; (b) 2 mmol of 1a,
0.6 mmol of ZnI2, 2 mmol of NEt3, 0.2 mL toluene, 30 1C, 1 MPa CO2
and different reaction times. Isolated yield.
93
94
transformed at low CO2 pressure. The time profile of the
conversion of 1a (Fig. 2b) was also studied, and a yield of
97% could be achieved in 21 h; namely, the reaction reached
equilibrium, and 1a was almost completely converted. Thus, the
optimal reaction conditions were obtained (Table 1, entry 10)
and the yield of the desired product reached 97% under mild
conditions.
5
95/94c
a
Reaction conditions: 2 mmol substrate; 2 mmol NEt3, 0.6 mmol ZnI2,
b
c
0.2 mL toluene, 30 1C, 1 MPa CO2. Isolated yields. Reaction condi-
tions: 60 1C, 28 h.
Catalyst generality
The reactions of CO2 with different substituted 2-aminobenzonitriles
1a–1e were then conducted under the optimized reaction conditions
using ZnI2/NEt3 as the catalyst, and the optimized reaction times
and the isolated yields of the target products are summarized in
Table 2. In general, the ZnI2/NEt3 system could promote the reaction
of CO2 with 2-aminobenzonitrile with different substituents under
mild conditions, and high yields could be obtained.
It was found that the ZnI2/NEt3 system was effective to
catalyze 2-aminobenzonitriles with different substituents, and
satisfactory yields of the corresponding products 2a–2e were
obtained. Moreover, the reactivity of the reaction depended on
the electronic effects of the substituted R group. In other words,
when R was an electron-donating group such as a methoxy
group, the substrate could be completely converted within 21 h
(Table 2 entry 2); when R was a halogen with an electron-
withdrawing effect, a significantly longer time was required to
complete the reaction (Table 2, entries 3–5).
Fig. 3 1H NMR spectra of 2-aminobenzonitrile in different catalyst systems.
(a) 1a; (b) 1a/ZnI2; (c) 1a/NEt3; (d), 1a/ZnI2/NEt3 ([D6]DMSO, 298 K).
obviously, and the chemical shift changed to 6.88 (Fig. 3c),
when NEt3 was added. Moreover, when ZnI2 was further added,
Reaction mechanism
As discussed above (Table 1), Zn(II) plays an important role in the chemical shift of the H atom of NH2 in 1a/ZnI2/NEt3
catalyzing this reaction. To further clarify the roles of ZnI2 and (Fig. 3d, d = 6.89) also increased; the degree of the increase
NEt3, the substrate 1a and mixtures of 1a/ZnI2, 1a/NEt3 and was similar to that of 1a/NEt3, suggesting that NEt3 played the
1a/ZnI2/NEt3 were examined by 1H NMR analysis, and the results main role in activating the NH2 in 1a. These results indicate
are given in Fig. 3. It was found that the 1H signal of NH2 in 1a that NEt3 alone can catalyze this reaction; this is inconsistent
was a sharp singlet peak that appeared at d = 6.00 ppm (Fig. 3a). with the experimental results, in which the reaction did not
1
The H signal of NH2 in the mixture of 1a/ZnI2 (Fig. 3b) was occur with NEt3 alone (entry 3 in Table 1). Dyson et al.23 found
similar to that of NH2 in 1a. These results indicate that ZnI2 that the basicity of the catalyst can influence its efficiency.
alone cannot activate the NH2 group of 1a; therefore, the Therefore, the basicity of NEt3 may be not strong enough to
transformation of CO2 did not occur with ZnI2 alone, which promote this reaction under our optimized reaction conditions.
is consistent with the experimental results in entry 2, Table 1. To further prove our speculation, the reaction of CO2 and
1
However, it was found that the H signal of NH2 in 1a shifted 2-aminobenzonitrile at 80 1C and 2 MPa using NEt3 alone as
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leading to strong nucleophilic ability of the N atom of the NH2
in 2-aminobenzonitrile. At the same time, CO2 was also activated
with NEt3 to form the carbamate salt. As a result, the N with
strong nucleophilic ability could perform a nucleophilic attack on
the C atom of CO2 to form the intermediate as well as the
[HNEt3]+ cation. Subsequently, the O atom attacked the C atom
in the CRN bond more readily because of the activation of the
CRN bond by ZnI2(NEt3) and further formed a quinazolide
anion. Finally, the quinazolide anion extracted the proton from
[HNEt3]+ to form the target product, and the catalytic system
could be recovered for the second cycle.
Fig. 4 13C NMR spectra of 2-aminobenzonitrile in different catalyst
systems. (a) 1a; (b) 1a/ZnI2; (c) 1a/NEt3; (d) 1a/ZnI2/NEt3 ([D6]DMSO, 298 K).
Conclusions
In conclusion, we found that inexpensive and easily available
ZnI2 and NEt3 can effectively synergistically catalyze the reactions
of CO2 and 2-aminobenzonitrile substrates to form quinazoline-
2,4(1H,3H)-diones at room temperature and low CO2 pressure,
and the yields of the target products could be up to 97% under
optimal conditions. Further experiments indicated that combining
ZnI2 with NEt3 could activate both the amino and cyano groups. We
hope that this study will provide new ideas and methods for
reactions involving amino and cyano groups.
the catalyst was carried out, and the yield of 2a increased to
29% within 6 h. These results suggest that NEt3 can activate
NH2 in 1a but that this reaction cannot proceed smoothly
without ZnI2 under our optimized reaction conditions (30 1C
and 1 MPa).
Therefore, the role of ZnI2 in the reaction was explored, and
13C NMR experiments of the substrate 1a, 1a/ZnI2, 1a/NEt3 and
1a/ZnI2/NEt3 were also carried out (Fig. 4). The 13C signal of
CRN in the mixture of 1a/ZnI2 (Fig. 4b) was similar to that of
CRN in 1a, indicating that the insoluble ZnI2 could not
activate CRN. The chemical shift 13C signal of the C atom of
CRN in 1a changed to 93.56 (Fig. 4c) when NEt3 was added,
which may be caused by the electronic effect of NEt3 on the C
atom of CRN in 1a. However, the 13C signal of CRN in 1a
shifted more obviously when ZnI2/NEt3 was added (Fig. 4d). Lei
et al.26 and Ma et al.27 reported that combining ZnI2 with NEt3
could form zinc complexes using experimental and theoretical
calculation methods, respectively. Therefore, the above results
indicate that the zinc complexes formed by ZnI2 and NEt3 can
effectively activate the CRN bond in 1a and further promote
the reaction under milder conditions (Table 1, entries 9 and 10).
Therefore, on the basis of the experimental results of this
study and related knowledge in the literature,23 a possible
reaction mechanism by which ZnI2/NEt3 promote the reaction
of CO2 with 2-aminobenzonitrile was proposed and is shown in
Scheme 2. Firstly, the amino hydrogen was activated by NEt3,
Conflicts of interest
There are no conflicts to declare.
Acknowledgements
The authors gratefully acknowledge partial financial support from
the National Natural Science Foundation of China (U1607123,
21901183 and 21773170), the Yangtze Scholars and Innovative
Research Team of the Chinese University (IRT_17R81) and the
Scientific Fund Project of the Education Committee of Tianjin,
China (2017KJ015).
Notes and references
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Scheme 2 The proposed mechanism of the ZnI2/NEt3-catalyzed trans-
formation of CO2 and 2-aminobenzonitrile to quinazoline-2,4(1H,3H)-
dione.
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